Keywords

Introduction

Patients who undergo surgical repair following aortic dissections have multiple hemostatic abnormalities due to numerous factors that contribute to coagulopathy and bleeding [1]. Anticoagulation and its reversal, exposure to extracorporeal circulation, tissue injury due to blood exposure in the false lumen, and further acquired defects [2] can all contribute to impaired hemostasis. Bleeding management in this patient population requires a multimodal approach [3, 4]. Developing specific bleeding management strategies and algorithms to guide transfusion decisions is an integral part of patient blood management which not only reduce allogeneic blood transfusions but optimize clinical care [5, 6]. Cardiac surgical patients undergoing aortic dissection repair are exposed to extensive surgery and often long cardiopulmonary bypass times, which place them at high risk for developing coagulopathy [7]. This chapter will review therapies focused on this patient population, including coagulation testing, blood product transfusion, and pharmacologic strategies to decrease bleeding.

Coagulation Testing

In patients who are bleeding following aortic surgery, coagulation testing is important to help define contributing hemostatic defects. Although standard laboratory coagulation tests are typically available (i.e., prothrombin time, partial thromboplastin time, platelet counts, fibrinogen levels), these have limitations with regard to specificity and reporting time. As a result, viscoelastic testing with the use of thromboelastography (TEG) or thromboelastometry (ROTEM) is increasingly used in bleeding management as it examines multiple aspects of the hemostatic system. Since whole blood is used for these tests, their samples require reduced preparation compared to standard laboratory tests, and thus reduced time, before actionable information can be obtained.

In cardiac surgical patients, impaired platelet function, in addition to reduced numbers, is a significant cause of bleeding [8]. However, platelet specific function testing is not widely available despite the use of viscoelastic testing and other point-of-care (POC) analyzers such as VerifyNow® and PFA-100®. POC platelet tests have not been validated in acutely bleeding patients since thrombocytopenia and hematocrit significantly influences their reported values. Even with standard TEG and ROTEM, it is important to understand that results are also affected by platelet number, and not function, due to the activators within the test (e.g., kaolin, tissue factor). Until better platelet function testing for the post-CPB period is developed, platelet transfusions for assumed dysfunction will continue to be administered empirically or based on platelet numbers [9].

Despite the lack of studies supporting platelet function tests in the perioperative management of cardiac surgical patients, multiple studies have shown that using pre-determined algorithms can decrease bleeding and transfusion requirements after cardiac surgery. Transfusion algorithms based upon objective measurements decrease the empirical administration of hemostatic factors [10]. Furthermore, algorithms based upon POC viscoelastic testing have been shown to reduce bleeding, the need for allogeneic transfusions, returned to the operating room for bleeding, and overall cost of transfusional therapy in aortic dissection patients [11]. An example of a viscoelastic tracing is provided in Fig. 1.

Fig. 1
figure 1

Examples of normal and hypocoagulable viscoelastic tracings. These are 2 tracings from a TEG® 5000 machine (Haemonetics, Braintree, MA). Although this is a static image, it should be noted that the tracing develops over time and can be read in a dynamic fashion. The top tracing (“Baseline”) depicts a normal coagulable state, while the bottom one (“Post CPB”) shows hypocoagulability. Measured components are depicted in color with their solid lines depicting the final value and the dashed reference lines representing the normal range. The R time (orange) is measured in minutes and represents initial thrombin generation and fibrin formation. The K time (green) is the amount of time for the clot strength to reach 20 mm in amplitude and represents a measure of fibrin build-up. The angle (blue) is formed by a tangential line to the curve at the K time and provides information on the speed of fibrin cross-linking. MA (purple) is the maximum amplitude of the clot strength and reflects fibrin and platelet interactions. The black numbers are derived from the curve and calculated. A: clot amplitude at any given time along the curve. PMA: projected MA, with a value of ‘0.0’ meaning the clot is likely to reach an MA in normal limits and a value of ‘1.0’ indicating it is unlikely. G: shear elastic modulus strength of the clot which is derived from MA. CI: coagulation index, which is a TEG® value calculated from the measured values to provide a summary of coagulability; CI >3.0 is indicative of hypercoagulability and a CI< –3.0 indicative of hypocoagulability. Fibrinolysis is not depicted on these curves (tracings were each stopped after ~50 min) since the patient was already receiving antifibrinolytic therapy, which is typical in cardiac surgery. EPL: estimated percent lysis at 30 min after MA reached and is continually updated until LY30 point is reached. LY30: percent lysis at 30 min after MA reached

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While POC tests have gained widespread use, most institutions have internally developed their own algorithms using these devices. In many randomized studies, point-of-care testing and transfusion algorithms decrease transfusions and improve hemostasis [10, 12,13,14,15]. However, different POC platforms have been used in these studies, along with different transfusion triggers. This is why meta-analyses of viscoelastic POC devices tend to show minimal effects [16,17,18]. Therefore, it is not clear whether the actual testing devices or the algorithms, which guide transfusion and decrease empirical administration, have the largest impact on reducing blood product usage.

Transfusion Therapy and Transfusion Guidelines

Multiple studies continue to define the role of transfusional therapies in acute bleeding in cardiac surgery. Unfortunately, most of the studies to date have focused on red blood cell (RBC) transfusions and defining the ideal hemoglobin as a transfusion trigger. There is less objective data available that evaluates the role of hemostatic blood components, which include fresh frozen plasma (FFP), platelets, and cryoprecipitate. Despite few controlled trials, there are an increasing number of guidelines and practice documents for bleeding management in cardiac surgical patients [19, 20]. Although these guidelines are reported as generally applicable recommendations, there are also other important considerations regarding the use of specific blood products in cardiac surgical patients that need to be considered. The rationale for the transfusion of individual blood components will be addressed in the following sections.

Red Blood Cells

Although many studies have focused on a specific hemoglobin trigger in cardiac surgery, multiple factors should be assessed when deciding on RBC transfusions in aortic dissection surgery. With acute hemorrhage, the rate of bleeding, which can be quite high in these situations, much be taken into account [21]. Transfusion decisions when hemoglobin concentrations are approximately 7–10 g/dL should be based on any potential or continuing bleeding rate and magnitude, and the intravascular volume status [21].

In general, the number of patients being transfused RBCs during cardiac surgery has significantly decreased over the past decade [22]. In a large, multi-center, randomized study, the TRICS III trial demonstrated a ‘restrictive’ (Hgb <7.5 g/dL) transfusion trigger was non-inferior to a ‘liberal’ trigger (Hgb <9.5 g/dL in the ICU) with respect to important patient outcomes [23]. It should be noted, however, that few patients in transfusion trials are undergoing aortic surgery, which is often an emergency and may be complicated by other undiagnosed patient co-morbidities and underlying coagulopathies. Hemoglobin triggers for RBC transfusion are not to be taken as absolute indications, and patients undergoing aortic dissection repair should be transfused if signs of inadequate perfusion are present.

Fresh Frozen Plasma (FFP)

FFP is overused in most surgical patients, often because of empirical therapy or to treat abnormal prothrombin times (PT) and/or partial thromboplastin times (PTT). Although these standard coagulation tests are used clinically to evaluate bleeding, they do not reflect bleeding in surgical patients and can be abnormal in patients who are not bleeding. Despite the extensive use of FFP, there is no data supporting its efficacy outside of trauma patients requiring massive transfusion [24]. Analyses of randomized controlled trials have been unable to demonstrate consistent evidence of benefit for plasma in most clinical scenarios [25]. The use of plasma to treat elevated international normalized ratios (INRs), especially when the INR is less than 1.7, is problematic since the INR of the FFP itself is about 1.5 [26]. Paradoxically, the overuse of FFP is therefore more likely to result in dilution and exacerbation of coagulopathy. The use of PCCs is now preferred over FFP for reversal of vitamin K antagonists [27].

This is not to say that FFP has no role in the treatment of aortic dissection patients. It has been well demonstrated that multiple plasma proteins, including coagulation factors and anticoagulation factors, significantly fall during aortic surgery with prolonged CPB [28]. FFP has a role in restoring these important proteins, although its use should be judicious. In situations of massive transfusion (see below), FFP is recommended as part of a balanced resuscitation. Although rare, catastrophic thrombosis following cardiac surgery can happen when only pro-coagulant therapies are administered following prolonged CPB [29]. More research is needed to determine the role of FFP in preventing this deadly event.

Cryoprecipitate

Cryoprecipitate is obtained from thawing FFP. The proteins that precipitate in a small volume include fibrinogen, factors VIII, XIII, and von Willebrand factor. Prior to administration, individual units of cryoprecipitate from multiple donors are pooled in the blood bank and administered usually as 5–10 units. Although initially developed for treating hemophilia due to its high factor VIII levels, the primary use of cryoprecipitate currently is to replete fibrinogen levels when specific fibrinogen concentrates are not available, or for acquired Factor XIII deficiency [30].

In Europe and other countries, cryoprecipitate is not available, and specific purified fibrinogen concentrates are used to treat bleeding. In the current era, the target hemostatic level of fibrinogen is 150–200 mg/dL (1.5–2.0 g/L), but the normal fibrinogen levels in plasma range from approximately 200–400 mg/dL and higher. Fibrinogen is critical to clot strength, and fibrinogen repletion for aortic surgery has been extensively studied and will be discussed later in factor concentrates. The levels of fibrinogen less than 100 mg/dL (1 g/L) can a prolong the clot-based coagulation tests PTT and PTT, and FFP administration is unlikely to correct. Cryoprecipitate or other methods of fibrinogen repletion should be considered in patients following aortic surgery as part of a multimodal protocol to manage bleeding [31].

Platelets

One of the major causes of bleeding in aortic surgery is both platelet dysfunction due to activation and extracorporeal circulation, as well as thrombocytopenia due to dilution and consumption. As previously stated, monitoring platelet function in acutely bleeding patients is problematic. As a result, platelets are administered based on a platelet count, as well as empirically administered when patients are bleeding. Most platelets transfused are obtained from single donors by apheresis or, alternatively, pooled multi-donor concentrates.

Following cardiac surgery, including aortic surgery, most transfusion algorithms suggest a threshold for platelet administration to be less than 100,000/μL, which is similar to neurosurgical procedures. As a reminder, normal platelet counts are 150,000–400,000 platelets/μL. Although viscoelastic testing is thought to assess platelet function, this is highly dependent on what activators are used, as well as fibrinogen levels.

Massive Transfusion

In aortic surgical patients, extensive bleeding may occur that requires large volume transfusions. This is often referred to as ‘massive transfusion,’ which is defined as the acute replacement of more than one blood volume or more than 10 units of PRBC within several hours [32, 33]. Treatment of the coagulopathy should include volume replacement, normothermia, resolution of acid-base abnormalities, and blood component therapy.

Most aortic surgical centers who routinely perform these procedures have protocols and facilities that are capable of providing allogeneic blood products as well as factor concentrates in a timely manner. However, in patients who have major bleeding, using fixed ratios of 1:1:1 for RBCs, plasma, and platelets, is standard management and part of damage control resuscitation [34]. Additionally, because of fibrinolysis, an antifibrinolytic should be considered in the bleeding cardiac surgical patient. Further management strategies include targeting fibrinogen levels in the form of cryoprecipitate or fibrinogen concentrates [34]. However, point-of-care monitoring and other goal-directed therapy can follow with fibrinogen levels and facilitate additional potential therapeutic approaches. The role of off-label use of factor concentrates to manage bleeding that cannot be controlled by conventional measures is still evolving (see below).

Adverse Effects of Transfusions

Allogeneic blood product transfusions are extensively used in aortic surgical patients, of which potential acute adverse effects include hypersensitivity reactions, sepsis, acute respiratory failure defined as transfusion-related acute lung injury (TRALI), and even volume overload describe is transfusion associated circulatory overload (TACO) [35,36,37]. In general, the higher the quantity of blood products transfused, the greater probability of developing acute respiratory distress syndrome (ARDS) [38].

Pharmacologic Therapies

Multiple systemic and topical pro-hemostatic agents are used during cardiac surgery. One of the unique aspects in this patient population is the ability to preemptively treat patients for potential bleeding problems, specifically with antifibrinolytic agents. The multiple agents used will be reviewed in this section.

Antifibrinolytic Agents

One of the mainstay therapies for both preventing and treating hemorrhage in patients following aortic surgery is the use of antifibrinolytic agents. There are multiple causes and initiation of fibrinolysis, both due to cardiopulmonary bypass as well as the activation that occurs following aortic dissection [39,40,41,42,43]. Efficacy in decreasing bleeding and transfusion is well established, as noted by the guidelines published by the Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists [44].

The current antifibrinolytic agents used are the lysine analogues: epsilon aminocaproic acid (EACA) and tranexamic acid (TXA). Both occupy the lysine binding site of plasminogen, preventing it from interacting with fibrin [45]. An extensive database supports the efficacy of antifibrinolytic agents in cardiac surgery to decrease bleeding and transfusion [46]. Although TXA is the primary agent used worldwide, it does come with potential for causing seizures, which is likely a dose-dependent effect [47]. Large scale clinical trials in CABG patients have suggested that cumulative doses above 50 mg/kg should be avoided [48]. Given that the risk of seizures may be increased when circulatory arrest is used, many clinicians often use EACA in this setting despite its potential to have an increased risk of renal failure and fewer studies in cardiac surgical patients [49, 50].

Protamine

One of the benefits of heparin anticoagulation is that it is acutely reversible with protamine, a highly basic peptide isolated from salmon sperm that binds heparin by forming a simple acid-base interaction [51]. Protamine rapidly reverses heparin to allow clot formation. Protamine can cause adverse reactions, including anaphylaxis, acute pulmonary vasoconstriction, and right ventricular failure, and hypotension [51]. Different reactions to protamine have been reported ranging from minimal cardiovascular effects to life-threatening cardiovascular collapse. Risk factors for protamine reactions have been reported to be allergies to NPH insulin and men who have had vasectomies, while aspirin administration may be protective [52].

Protamine administration for heparin reversal after cardiac surgery is often highly empirical administering large doses of protamine for persistent bleeding when bleeding is related to multiple other factors. What should be remembered is that protamine itself can inhibit platelet aggregation and prolong the ACT. Multiple studies report that excess protamine beyond what is needed for actual reversal decreases clot strength. Clinicians’ routine administration of additional protamine to treat a prolonged activated clotting time may actually further increase clotting time and contribute to excess bleeding [53]. Therefore, approaches to avoid excess protamine using heparin protamine titrations or fixed protamine doses based on time and duration of cardiopulmonary bypass are important as part of a multimodal strategy [54].

Desmopressin

Desmopressin (also called DDAVP) is an analog of vasopressin that releases large von Willebrand factor multimers from their storage site in endothelial cells [55,56,57,58]. Rapid administration can cause hypotension, and as a result, it should be given slowly using doses of 0.3 mcg/kg to avoid vasodilation [59, 60]. despite its extensive use in cardiac surgical patients, 18 trials of desmopressin in 1295 patients undergoing cardiac surgery only demonstrated small reductions on blood loss with ~115 mL median volume reduction), and little data supporting any efficacy [60, 61]. The best use for DDAVP in cardiac surgery may be in patients with impaired renal function.

Fibrinogen Concentrate

Fibrinogen is a critical coagulation factor that has been extensively studied in aortic surgical patients for repletion using fibrinogen concentrates. Fibrinogen levels also have been reported to be predictors of perioperative bleeding [62, 63]. As previously discussed, both cryoprecipitate and purified fibrinogen concentrates are the two major methods of repeating fibrinogen levels. However, fibrinogen concentrate has been the focus of most trials to date.

In one of the first prospective, randomized, and blinded studies of patients undergoing elective aortic replacement surgery, 61 patients were randomized to receive either fibrinogen concentrate or placebo [64]. Fibrinogen levels were determined using viscoelastic monitoring with FIBTEM testing following separation from cardiopulmonary bypass and protamine reversal. Fibrinogen concentrate administration reduced transfusions compared to placebo (2 units versus 13 units), and transfusion avoidance occurred in 13 of 29 patients receiving fibrinogen concentrates compared to none of the placebo-treated patients. Of note, the FIBTEM test is a point of care viscoelastic testing method that removes the platelet contribution for clot formation by inhibiting platelet activation to evaluate fibrinogen levels or abnormalities in clot formation, and generally correlates with laboratory-based fibrinogen assays (Clauss assays).

Other retrospective studies and prospective studies have reported fibrinogen concentrate administration and aortic surgery reduces bleeding and the need for transfusions both intraoperatively and postoperatively [65,66,67,68,69]. In another study of patients undergoing elective aortic valve and ascending aorta replacement, fibrinogen concentrate reduced 24-h postoperative bleeding and blood product administration [66]. Bleeding and transfusion were also reduced in a similar retrospective evaluation of fibrinogen repletion using purified concentrates and guided by of-care fibrinogen measurements using FIBTEM for post-bypass bleeding following thoracoabdominal aortic aneurysm repair [67]. The need for subsequent blood product transfusion was reduced in these patients, as was 24-h chest tube drainage volume.

Because of the success of reducing both bleeding and allogeneic blood transfusion using fibrinogen concentrates, the concept was expanded to a worldwide multicenter randomized clinical trial that evaluated 519 patients from 34 different medical centers to fibrinogen replacement using a five-minute bleeding mass to determine whether patients would be treated. A total of 152 patients met inclusion criteria for fibrinogen repletion with similar median and interquartile ranges of pretreatment 5 min bleeding masses of 107 (76–138) grams in the fibrinogen group compared to placebo with 91 (71–112) grams. In the fibrinogen concentrate and placebo groups, respectively (P = 0.13). Of note is that patients who received fibrinogen concentrates received more allogeneic blood products in the first 24 h postoperatively: 5.0 units (2.0–11.0), when compared with placebo, 3.0 (0.0–7.0). Most of the prior studies that showed marked efficacy of fibrinogen concentrates reducing bleeding were from a single European center with a large active aortic surgical program. In the large multicenter study, low bleeding rates and normal fibrinogen levels, along with the inability to follow a complex transfusion algorithm, likely influenced the results. The overall message for the clinician is that preemptively raising fibrinogen levels alone without treating the underlying coagulopathy is not likely beneficial and levels should be targeted as discussed above.

Recombinant Factor VIIa (rFVIIa)

Recombinant activated factor VII (rFVIIa) is approved in most countries for the treatment of bleeding episodes and perioperative management in adults and children with hemophilia A or B with inhibitors, congenital Factor VII (FVII) deficiency, and Glanzmann’s thrombasthenia with refractoriness to platelet transfusions, with or without antibodies to platelets. However, clinicians have used it off label for intractable bleeding, including in cardiac surgical patients.

In one of the first prospective trials, Gill et al. enrolled patients following cardiac surgery who were bleeding more than 200 mL/h and had not been otherwise treated [70]. In this phase II, dose-escalation study, 35 patients were randomized to receive rFVIIa at doses of 40 mcg/kg rFVIIa, 69 patients received 80 mcg/kg rFVIIa, and 68 patients received placebo. Although the primary endpoint was serious adverse events, secondary end points included rates of re-exploration, additional transfusions, and amount of blood loss. There were no statistically significant differences in adverse events among the groups however, significantly fewer patients treated with rFVIIa group underwent re-exploration for bleeding (P = 0.03) or required allogeneic transfusions (P = 0.01) [70].

A more extensive safety study of 4468 subjects that included 4119 patients and 349 healthy volunteers reported a higher rate of arterial thromboembolic events among those subjects who received rFVIIa compared to placebo (5.5% vs. 3.2%) [71]. Interestingly, venous thromboembolic events were similar (5.3% vs. 5.7%). It should be noted that major bleeding in cardiac surgical patients increases the risk of serious adverse events, including operative mortality, as does increased transfusion of blood products [72]. Therefore, when evaluating ‘rescue therapies’ such as rFVIIa, these risks must be weighed against potential complications of the therapy. In patients major aortic surgery with refractory bleeding, rFVIIa as salvage therapy has been reported and recommended [73].

Prothrombin Complex Concentrates

Prothrombin complex concentrates (PCCs) are purified, freeze-dried coagulation factors derived from pools of plasma that include factors II, VII, IX, and X in concentrations that depend on the manufacturer [74]. In the United States, both three factor and four factor PCCs are available. The three factor PCCs were originally for hemophilia therapy and included factor IX products that include Profilnine SD [Grifols, Barcelona, Spain], Bebulin VH [Baxter], and Factor Eight Inhibitory Bypassing Activity(FEIBA) VH [Baxter] [75]. Bebulin and Profilnine contain low levels of factor VII, while FEIBA contains the activated form of VII (VIIa). Four-Factor PCCs are approved for warfarin and other vitamin K antagonist reversal. Three-factor PCCs are often administered for bleeding rather than vitamin K antagonist reversal and used for off-label indications, including bleeding in surgical patients. Kcentra (CSL Behring) is the only four component PCC available in the United States but is called Beriplex P/N in other countries. Other four component PCCs available in most countries and include Octaplex (Octapharma, Vienna, Austria) [75,76,77,78,79]. While PCCs have been around for decades, modern agents differ in that most also include low levels of anticoagulants including Protein C and Protein S, as well as antithrombin.

In Europe, viscoelastic monitoring is used extensively for goal-directed bleeding management, and algorithms for bleeding in cardiac surgical patients routinely include the use of four component PCCs, although the body of evidence for this is currently small. Retrospective evaluation of a large database reported that initial treatment using POC testing with PCCs, decreased bleeding as well as thrombotic complications [80]. There was also a reduced need for allogeneic transfusion with FFP, but platelet transfusions were increased [80].

Much like rVIIa, PCCs have also been reported as rescue therapy for life-threatening bleeding refractory to conventional treatment. One report of 25 patients who received FEIBA as rescue therapy included aortic root replacement and heart transplants. Following a mean FEIBA doses of 2154 units, FFP and platelet transfusions decreased without need for re-exploration [81]. One Canadian multicenter phase II study is underway, the Factor Replacement in Surgery Trial (NCT04114643), to better evaluate the role of factor concentrates versus FFP in cardiac surgical bleeding.

Topical Hemostatic Agents

In aortic surgical patients, hemostatic agents are often applied as adjunctive measures to promote hemostasis. Multiple agents have been reported in cardiac surgical patients, and commonly encountered ones are summarized in Table 1. They are typically applied directly to the site of oozing within the surgical field. In patients with active bleeding, the application of such agents can be challenging, which may limit their efficacy. Although much of the data evaluating these agents is from retrospective analyses, there are some randomized clinical trials that have been previously reviewed [82]. Topical agents can be broadly classified into those that provide a mechanical barrier, those that contain an active hemostatic agent, or those that combine both of these elements.

Table 1 Topical hemostatic agents commonly used in aortic surgery
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Mechanical hemostatic agents are used to provide a barrier at the site of bleeding to allow for potential hemostatic activation and provide a scaffold for the accumulation of critical hemostatic factors. Because they rely on the patient’s coagulation system, they should be left in place until clot forms. The most widely used agent of this type is simply bone wax, whose application is almost ubiquitous with sternal closure. Other agents are mainly derived from porcine gelatin or bovine collagen, which in its anhydrous form, can bind bleeding surfaces. Collagen sponges are similar to microfibrillar collagen but obtained from bovine tendon or skin.

Synthetic sealants are also applied to reduce bleeding in a mechanical fashion. A synthetic polyethylene glycol has been extensively used in Bentall thoracic aortic surgery [83]. For major aortic and other cardiac surgical patients, Coselli et al. examined the use a “bioglue” that contains bovine albumin with glutaraldehyde and reported improved hemostasis at anastomotic sites [84]. Despite the potential efficacy, glutaraldehyde may have the potential for tissue injury compared to other potential topical hemostatic products [85].

The compound for most active topical agents is thrombin, used either as a single therapy or combined by the surgeon with a mechanical agent (e.g., a gelatin sponge). The concept of topical thrombin is to locally activate the clotting cascade. Early topical thrombin preparations were bovine derived. Unfortunately, the xenogenic source induced antibody formation against human thrombin and factor V, causing potential hypersensitivity reactions as well as complex coagulopathic bleeding states. As a result, bovine thrombin is seldom used in the current era. The development of both purified and recombinant human thrombin has reduced these adverse reactions.

Therapeutic agents that combine both mechanical properties and have an active hemostatic agent fall into two categories: gelatin plus thrombin (often termed ‘flowable’ agents), and fibrin sealants. The gelatin used for flowable agents is either porcine or bovine derived and then combined with human thrombin. The product must be reconstituted when ready to use and is typically delivered via a specialized applicator. Fibrin sealants contain two critical hemostatic factors, thrombin, and fibrinogen. They can be administered as either a patch or in liquid form to provide local hemostasis, but require a relatively dry field to be effective. For these different agents, different sources of hemostatic factors are used in individual preparations and include human, bovine collagen and thrombin, and equine collagen. Fibrin sealants can also be mixtures of human fibrinogen, thrombin, and an antifibrinolytic agent to prevent clot lysis, traditionally aprotinin [86].

Summary

Coagulopathy and bleeding management requires a multimodal approach that includes fibrinogen repletion, providing appropriate procoagulants, and antifibrinolytic agents. When patients bleed, surgical sources of bleeding should also be considered, especially in an ICU setting. In addition to allogeneic blood transfusions, factor concentrates are increasingly management strategies to consider in treatment algorithms. With major hemorrhage, specific protocols for massive transfusion should be considered. Bleeding management algorithms in cardiac surgical patients are increasingly used that include this multimodal therapy along with as well as goal-directed management with point-of-care viscoelastic testing.